@article {1140,
	title = {Cell spread area and traction forces determine myosin-II-based cortex thickness regulation. [Central Imaging and Flow Cytometry Facility]},
	journal = {Biochim Biophys Acta Mol Cell Res},
	year = {2019},
	month = {2019 Jul 23},
	abstract = {<p>Actomyosin network under the plasma membrane of cells forms a cortical layer that regulates cellular deformations during different processes. What regulates the cortex? Characterized by its thickness, it is believed to be regulated by actin dynamics, filament-length regulators and myosin motor proteins. However, its regulation by cellular morphology (e.g. cell spread area) or mechanical microenvironment (e.g. substrate stiffness) has remained largely unexplored. In this study, super- and high-resolution imaging of actin in CHO cells demonstrates that at high spread areas (\&gt;450 μm), the cortex is thinner, better separated as layers, and sensitive to deactivation of myosin II motors or reduction of substrate stiffness (and traction forces). In less spread cells (\&lt;400 μm) such perturbations do not elicit a response. Myosin IIA{\textquoteright}s mechanosensing is limited here due to its lowered actin-bound fraction and higher turnover rate. Cofilin, in line with its competitive inhibitory role, is found to be overexpressed in these cells. To establish the causal relation, we initiate a spread area drop by de-adhesion and find enhanced actin dynamics and fragmentation along with oscillations and increase in thickness. This is more correlated to the reduction of traction forces than the endocytosis-based reduction in cell volume. Cortex thickness control by spread area is also found be true during differentiation of THP-1 monocytes to macrophages. Thus, we propose that spread area regulates cortex and its thickness by traction-based mechanosensing of myosin II.</p>
},
	issn = {1879-2596},
	doi = {10.1016/j.bbamcr.2019.07.011},
	author = {Kumar, Rinku and Saha, Sajjita and Sinha, Bidisha}
}
